Separation of solutes by continuous solvent extraction



June 10, 1952 J. D. A. JoHNsoN SEPARATION OF' SOLUTES BYCONTINUOUS SOLVENT EXTRACTION 2 SHEETS-SHEET l Filed Nov. 18, 1949 .WSR

June 10, 1952 J. D. A. JoHNsoN 2,599,836

SEPARATION 6F SOLUTES BY 4CONTINUOUS SOLVENT EXTRACTION Filed Nov. 18, 1949 2 SHEETS-SHEET 2 JM, fw

Patented June 10, 1952 SEPARATION OF SOLUTES BY CONTINUOUS SOLVENT EXTRACTION John Dobney Andrew Johnson, Dorking, England, assignor to v.Beecham Research Laboratories Limited, Betchworth, Surrey, England, a company of Great Britain Application November 18, 1949, Serial No. 128,167 In rGreat Britain November 29, 1948 (Cl. 26o-705) 6 Claims. 1

This invention relates to the separation -of solutes by vcontinuous redistribution between immscible or partially -miscible solvents.

Continuous counter-current lextraction has 1hiitherto vbeen carried out by permitting immiscible liquids Ito move continuously -in opposite directions in columns or through `a series of vessels, solute being redistributed between or transferred vcontinuously from the one solvent to the other in such a -way that it is removed from admixture with other solutes toa greater or lesser degree. In all published "processes k(except those detailed below) the solutes enter -t-he system lcontinuously and the effect -can be likened to the continuous stripping out of one or more Aoomponents `from the 4solute mixture. -For example, desirable'components of Aa crude oil are removable by permitting the Ycrude -oi-l to Imix with .a 'suitable solvent in aline mixer, -and t-hen allow- 'ing the `mixture to separate yinto .twol'ayers ina separator. The `two phasesthen move 'in opposite senses "to adjacent line mixers where the process repeated (Knox 'et aliae, JInd. Eng. Chem., '-1947, 39, "1573), Aand Aso on. Or 'phenols are removed continuously from coal tar liquors 'by countercurrent extraction with alkali I(Murdoch `and Cuckn'ey, Ind. Chemist, 1946, 22, 74,11).

Thev exceptions referred v'toabovefare apartially successful concentration of vitamin A by -Cornish et-aliae ('Ind. Eng. Chem., 1934, 26,397) who used 'a long tube 'broken lup into compartments, the mixture of solutes being introduced lat a lgiven point 'somewherenear the middle of -the tube, the solvents being introduced at opposite ends, and that -o`f Martin and Synge (Biochem. `J., 119.114, `35,'9'1') who'used a bank of-40 mixing vessels connected together by wide glass tubes which acted asseparators.

'Both-these method-s proved unsatisfactory because vthe mixers Aand. separators -did `not fform sufficiently discrete units, "because the :volumeloi theseparators `compared with that -of the .mixers was'ltoolgreat-or becauselof imperfect `se1; aration pf-phases.

According to the present invention there Eis lprovided. an improved process `for the vseparation 'of vsalutes -by continuous redistribution :between sdlventsfo'f the type wherein-a denitefquantity of a mixture of the -so`lutes is :initially introduced ginto .a separating plant -rand a first :solvent :is lcaused "to ow continuously through the plant `which lcontains, or f'through which vis -cause'd to Tflow in counter-current, a `second solvent lim- -niiscibleor partially miscible withth'e'lrst. 'The Trocess 'of the invention-ischaracterisedinfthat "the plant comprises a series of .units each consisting Y'of a mixer of relatively large capacity connected to .deliver its contents to a separator (distinct from the mixer) of relatively small capacity, the latter .being vconnected .todeliver ,the separated first solvent to the mixer `of 'the next succeed-ing unit and being connected to deliver the separated second solvent back to .the rst- Vmentioned mixer ror, in the case .of the second solvent being :caused to flow in .counter-current, `to Ithe 'mixerof :the preceding unit. In'thi-s'latter case the Amixers and separators may .be so .ar- -ranged `vthat the two solvents enter the'systemsat the twoends land leave at .twoopposite ends, ;.or the vessels and mixers may Vform a .closed system lin lwhich the two solvents .circulate in contrary directions.

The mixers .may be any suitable vessels in ywhich solventsYma-y be stirred or .otherwise agi-` tated 4to produce a homogeneous mixture, the delivery tov the separators being so arranged that the liquid passing from a mixer into anassociated separator is a representative .sample vof the liquid in that mixer at that time.

It will -be appreciated that the :inventionfhas two main variants, i. e. one in which the second solvent is passed through the plant in counterf current tothe .rst solvent, both solvents passing continuously out of vthe system or both beingretained 'in the system, and the other in'which `the second solvent only is retained;in the plant.

An embodiment of the rst variant of the ijn-v vention is .-diagrammatically lillustrated :in Fig- -ures -1fand 2 ofthe accompanying drawings y.and lan :embodiment :of the `second variant of the in.- vention is diagrammatically illustrated :in Figure 3 ofthe accompanying drawings.

Figures 4 and 5 vare graphs illustrating the separational rdistribution of 'salutes which is 4efectedby the :use of the plant of `Figure 11.

'Referring to Figure 1, the .plant comprises n Aunits each consisting .of amixer Mand 4a Sepa-A rator S, the .several mixers being denotedin the drawing by the reference M1, M2 Mn-and the severalseparators being denoted 'by theireference lletters S1,S2 Sn.

Thesolvent A lis introducedinto -the .mixer at one endof the plant, and leaves at theiseparator 'Si at 4the .other end of Vthe lplant. The Asolvent B enters at .the mixer M1 and leaves :the plant; at the separator Sn.

The arrows indicate the lines of flow ifrom lmixers to ,separators and 'from separators to 'mixers respectively. The Larrow between the mixer and separat-croi aparticular unit indicates ,3 a delivery of homogeneous mixture from the mixer to separator whilst the arrows connecting a separator to the mixers of the adjacent units indicate the flow of the portions of the mixture which are separated in that separator.

Referring to Figure 2 the plant comprises 1L units each consisting of a mixer M and a separator S, the reference letters in Figure 2 having the same significance as those in Figure 1. The plant contains a xed quantity of the first solvent and a xed quantity of the second solvent which are caused to travel in counter-current through the system in a manner indicated by the arrows.

It will be understood that the separators applicable to the systems indicated by Figures l,

2 and 3 may be of the gravity, centrifugal orV other type and that the flow of liquid is effected in some conventional manner.

It Will be noted that each mixer and its associated separator form a discrete unit and that there is no chance of a portion of the contents of one mixer passing into an adjacent mixer except after due separation in the separator associated with the first-mentioned mixer.

T'he mixture of solutes to be separated is initially introduced into one of the mixers which, ifthe plant be of the type indicated by Figure 1 is preferably in the central region; it is immaterial into Vwhich vessel of the system indicated by Figure 2 the solute is placed. When the iiow of the solvents is initiated the solutes will move according to their distribution coefficients. The solutes with values of distribution coefcients greater than `unity will move on the average in one direction, while those with coecients less than unity will move on the average in the otherdirection if the feed rates of the solvents are equal, but the rates at which the solutes move and the direction of movement depends on. the solvent feed rates and the particular values of distribution coefl'icients.

By choosing a sufficiently long system of vessels, that is a large number of units, solutes will be caused to issue from one or both ends of the system indicated by Figure 1, comparatively free from admixture with one another and in the systemindicated by Figure 2 the solutes will be found-.t predominate severally in vessels determined'by the time of operation of the plant.

The graph shown in Figure 4 indicates the separation'of three solutesV having respectively distribution coefficients in solvent B with respect to 'solvent A of 0.1, 1.0 and 10.0. |The curves in the igraph are marked with these distribution coefficients 1620.1, kzl and lc= and the ordinates of these curves show the concentrations of the solutes to which they relate in the respective mixing vessels of a plant in'accordance with Figure 1 which in this case is considered to contain 19 vessels. It will be understood that the curves indicate the separational distribution of the solutes at the end of a given period of time.

It will be noted that the'end vessels of the system are practically free of solute 1c=1 which, thereforehas shown little tendency to leave the system at all. On the other hand the separation of the solutes lc:0.l and 14::10 is substantially complete, theV former leaving the system at the one end and the latter leaving at the other end. 1

The behaviour of a system of the type indicated by Figure 2 is similar but the time of operation of the plant must be chosen with care since the separated components of the solute mixture 4 may tend to re-mix if the period of operation is prolonged.

The example illustrated by the graph of Figure 4 applies to solutes .with widely different values of lc in a system of the type indicated by Figure 1 Where the number of mixers and separators is large. Solutes with closer values of lc would require a more extended system of vessels to ensure such sharp separation and this is indicated in the graph of Figure 5 which relates to six solutes. The number of vessels in this case is an indefinitely large number and the direction of movement of the solutes is determined by their distribution coefcients and the feed rates of the solvents. The ordinates are related to the quantities of the solutes present. It will be noted that solutes tend to congregate in sets of vessels determined by their values of 7c. Complex mixtures of many solutes are therefore readily separable provided that a suflicient number of Vessels is included in the system.

It will be appreciated that as time goes on the Waves representing the solutes moving to the left will move progressively in that direction, While those moving to the right will move progressively contrariwise so that the several solutes can be successively eliminated from each end of the system each in a reasonably good state of purity provided that consecutive solutes eliminated from a given end diifer suiciently with regard to their 7c values.

Referring now to Figure 3 the plant comprises a series of mixers M1, Mz Mn and a series of separators S1, S2 Sn as in Figure 1.

The solvent A is introduced into mixer M1 at one end of the plant and leaves at the separator Sn at the other end of the plant. Unlike the previous example, however, solvent B does not ow throughout the length of the plant, different portions of solvent B being confined to separate units. The arrows from mixer to separator indicate a delivery of homogeneous mixture whilst the arrows from separator to mixer represent the flow of separated portions of the liquid as before.

Initially all the mixers are partly filled with solvent B, and preferably they are almost completely filled therewith. When solvent A is being fed through the system, a homogeneous mixture of A and B rich in B, will be be produced in each mixer, atypical sample `of the mixture being continuously delivered to the associated separator wherein A and B separate out into layers, B being then returned to the same mixer and A being passed on to the next succeeding mixer. v

A batch of solute is now introduced into mixer M1 whereupon the components having different distribution coeiiicients between A and B distribute between the two solvents A and lB accordingly. VIi. the distribution coeflic'ient of a component of the solute in A with respect to B is much greater than unity, little ofitl will dissolve in B vin any mixer and the bulk of this component will pass through the plant at a fairly rapid rate. For solute components whose distribution coefficients are not much greater than unity, however, there will be a delaying action on their fiovv through the plant since a certain amount will dissolve in AB and after separation will be vreturned tothe same mixer again leaving only that portion which has dissolved in A to continue throughthe plant.

Ultimatelyhoweversubstantially all the solute alwayshdissolves a; certain amount of solute in any unit and car-ries it on to the next unit, Whatevergits distribution coefficient.

After the introduction of lsolute into M; the concentration of any solute component in any of the mixers Mz, Ms Mn rises to a maximum and then falls again and these concentration maxima will pass along the plant at a rate directlyl proportional to the distribution coeilicients of the components towhich'they relate, if the mixers 'are initially practically filled with B. Thus with a plant consisting of a large number of units the concentration maximajwill become well spaced and the emergent solvent A will contain substantially only one solute component at a time, provided that the lc valuesl of 'theseveral components are not too close together, and in this way very complete separations may be carried out.

The invention may of course be used tol separate the components of many different types of mix such as the separation of the various penicillins normally produced by mould growth and in the separation of specific amino-acids from protein hydrolysates.

Each of the processes illustrated by Figures l, 2 and 3 may be varied by altering the feed rates of the solvents until insuflcient time is allowed for the contents of the mixers to reach the equilibrium which `would be otherwise reached if the feed rates of solvents were suiliciently slow. Thus two solutes having identical values of k may be separated if the rate of equilibration of the one solute between the two solvent phases is different from the rate of equilibration of the other solute between the two solvent phases.

The following examples illustrate but do not limit the invention.

EXAMPLE 1 Separation of succz'm'c and oalic acids A mixture of 25 grams of oxalic acid and 25 grams succinic acid was placed in the th vessel of a series of 19-vessels arranged according to Figure 1. The solvents used were n-butanol saturated with water and water saturated with n-butanol. With a flow rate ratio of 0.615 (butanol water) the succinic acid issued approximately 82 per cent. pure and the oxalic acid 99 per cent. pure.

EXAMPLE 2 Isolation of glutamic acid ,from a protein hydrolysate A casein hydrolysate freed as far as possible from glutamic acid by other means, was neutralised and subjected to extraction in an apparatus of the type indicated by Figure 2 and comprising vessels. Using butanol as moving solvent phase, unwanted amino-acids and other material were largely removed from vessels I, 2 and 3 thus permitting the isolation of a further l0 per cent. of the glutamic acid originally present, from the contents of these three vessels.

When we specify herein that the separator must be distinct from the mixer, we mean that the two parts must be distinct in function. The separator and mixer may of course be embodied in a unitary structure but they will be quite distinct from each other within that unitary structure.

Iclaim:

1. A process for the separation of batch-fed solute mixtures by continuous redistribution between .solvents ink a :separating system, comprising a vseries of 'unitary zones each containing 'a mixing sub-zone in which uniform composition is obtained by mechanical agitation and a separating sub-zone in which separation is dependent upon the respective specific `gravi-ties of the separated Icomponents "and which 4sub-zone capable of containing only `a smallfquantity of liquid in comparison with that conta-ined in the mixingsub-zon'e, said sub-zones being distinct from one another, said yprocess being characterized in that a lbatchfof a mixture of solutes is introducedv into the system, a first solvent is caused to flow continuously through the system, and a second solvent not completely miscible with the first v`solvent is introduced into the system, the contents of each lmixing sub-zone being delivered to thel separating sub-zoneof the same unitary zone, the separated frstsolventfrom each separating subzone being delivered separately from .said lmixing sub-zone 'contents to the mixing sub-zone of the next succeeding unitary zone, and the separated second solvent from each separating sub-zone being delivered separately from said mixing subzone contents and from said first solvent to a mixing sub-zone of a unitary zone preceding that to which the separated iirst solvent is delivered.

2. A process for the separation of batch-fed solute mixtures by continuous redistribution between solvents in a separatingsystem, comprising a series of unitary zones each containing a mixing sub-zone in which uniform composition is obtained by mechanical agitation and a separating sub-zone in which separation is dependent upon the respective specific gravities of the separated components and which sub-zone is capable of containing only a small quantity of liquid in comparison with that contained in the mixing sub-zone, said sub-zones being distinct from one another, said process being characterized in that a batch of a mixture of solutes is introduced into the system and a first solvent is caused to flow'continuously through the system which initially contains a second solvent not completely miscible with the first solvent, the contents of each mixing sub-zone being delivered to the separating sub-zone of the same unitary zone, the separated rst solvent from each separating sub-zone being delivered separately from said mixingsub-zone contents to the mixing sub-zone of the next succeeding unitary zone, and the separated second solvent from each separating subzone being delivered separately from said mixing sub-zone contents and from said first solvent back to the mixing sub-zone of the same unitary zone.

3. A process as claimed in claim 2 in which the second solvent is introduced into each of the unitary zones and the first solvent is introduced continuously at one end of the system and withdrawn at the other end, the mixture of solutes being introduced at the same end of the system as the first solvent.

4. A process for the separation of batch-fed solute mixtures by continuous redistribution between solvents in a separating system, comprising a series of unitary zones each containing a mixing sub-zone in which uniform composition is obtained by mechanical agitation and a separating sub-zone in which separation is dependent upon the respective specific gravities of the separated components and which sub-zone is capable of containing only a small quantity of liquid in comparison with that contained in the mixing sub-zone, said sub-Zones being distinct from one another, said process beingcharacterized in that a batch of a mixture of solutes is introduced into the system, a rst solvent is caused to flow continuouslyv through the system, and a second solvent not completely miscible with the first solvent is forced to flow continuously through the system in countercurrent to the rst solvent, the contents of each mixing sub-zone being delivered to the separating sub-zone of the same unitary zone, the separated first solvent from each separating sub-zone being delivered to the mixing sub-zone of the next.v succeeding unitary zone, and the separated second solvent from each mixing sub-zone being delivered to the mixing subzone of the preceding unitary zone.

5. A process as claimed in claim 4 in which the solvents are introduced one at each end of the system and withdrawn at opposite ends, the mixture of solutes being introduced into the system at a pointv remote from both ends.

6. A process as claimed in claim 4 in which the VREFERENCES CITED The following references are of record in the flle of this patent:

UNITED STATES PATENTS Number Name Y Date 708,494 Randall Sept. 2, 1902 863,062 Griswold, fJr Aug. 13, 1907 2,076,126 Guinot I ;i Apr. 6, 1937 2,079,511 Klar et al. May 4, 1937 OTHER REFERENCES Ind. and Eng. Chem., vol. 26, 1934, pp. 397-405. Biochem. J., 1941, vol. 35, pp. 91-1201. 

1. A PROCESS FOR THE SEPARATION OF BATCH-FED SOLUTE MIXTURES BY CONTINUOUS REDISTRIBUTION BETWEEN SOLVENTS IN A SEPARATING SYSTEM, COMPRISING A SERIES OF UNITARY ZONES EACH CONTAINING A MIXING SUB-ZONE IN WHICH UNIFORM COMPOSITION IS OBTAINED BY MECHANICAL AGITATION AND A SEPARATING SUB-ZONE IN WHICH SEPARATION IS DEPENDENT UPON THE RESPECTIVE SPECIFIC GRAVITIES OF THE SEPARATED COMPONENTS AND WHICH SUB-ZONE IS CAPABLE OF CONTAINING ONLY A SMALL QUANTITY OF LIQUID IN COMPARISON WITH THAT CONTAINED IN THE MIXING SUB-ZONE, SAID SUB-ZONES BEING DISTINCT FROM ONE ANOTHER, SAID PROCESS BEING CHARACTERIZED IN THAT A BATCH OF A MIXTURE OF SOLUTES IS INTRODUCED INTO THE SYSTEM, A FIRST SOLVENT IS CAUSED TO FLOW CONTINUOUSLY THROUGH THE SYSTEM, AND A SECOND SOLVENT NOT COMPLETELY MISICIBLE WITH THE FIRST SOLVENT IS INTRODUCED INTO THE SYSTEM, THE CONTENTS OF EACH MIXING SUB-ZONE BEING DELIVERED TO THE SEPARATING SUB-ZONE OF THE SAME UNITARY ZONE, THE SEPARATED FIRST SOLVENT FROM EACH SEPARATING SUBZONE BEING DELIVERED SEPARATELY FROM SAID MIXING SUB-ZONE CONTENTS TO THE MIXING SUB-ZONE OF THE NEXT SUCCEDING UNITARY ZONE, AND THE SEPARATED SECOND SOLVENT FROM EACH SEPARATING SUB-ZONE BEING DELIVERED SEPARATELY FROM SAID MIXING SUBZONE CONTENTS AND FROM SAID FIRST SOLVENT TO A MIXING SUB-ZONE OF A UNITARY ZONE PRECEDING THAT TO WHICH THE SEPARATED FIRST SOLVENT IS DELIVERED. 